1, 3-methano-h-cyclopropa (cd) naphthalene-4, 7-diones



United States Patent Ofifice 3,291,835 1,3-METHANO-H-CYCLOPROPA(cd) NAPHTHALENE-lfl-DHONES Hsing Yun Fan, Modesto, Calif., assignor to Shell Oil Company, New York, N.Y., a corporation of Delaware No Drawing. Filed Jan. 17, 1964, Ser. No. 338,304 9 Claims. (Cl. 260586) This application is a continuation-in-part of COpCllClll'lg application Serial No. 828,733, filed July 22, 1959, now.

abandoned.

This invention is concerned with and takes as its principal object the provision of a novel class of polyhydromethanocyclopropanaphthalenediones, characterized by the following ring structure:

R being hereinafter defined, and the method of making these novel compounds.

The present invention also concerns and takes as an object compositions containing these compounds and their use as biocides, particularly against nematodes, fungi, bacteria and deleterious microorganisms.

The present invention is particularly concerned with 3a substituted 1a,2,3,3a tetrahydro 1,3 methanolH-cyclopropa-(cd)naphthalene-4,7-diones having the following structural formula:

wherein each R, independently, represents hydrogen, middle halogen, unsubstituted alkyl of from one to ten carbon atoms or alkoxy of from one to ten carbon atoms, the alkyl moiety thereof being unsubstituted, R represents unsubstituted or monoor poly-(middle halogen)- substituted alkyl of from one to ten carbon atoms, allyl, benzyl, methoxyethyl, hydroxyethyl, dihydroxypropyl, tetrahydrofurfuryl, tetrahydropyranyl and 2,2-dimethyl- 1,3-dioxolan-4-ylmethyl. The alkyl groups represented by R, R and the alkoxy groups represented by R can each be of straight-chain configuration, or of branchedchain configuration.

Of these compounds, the subclass wherein there is an olefinic double bond between the carbon atoms in the 5- and 6-positions and at least two of the Rs are middle halogen is of particular interest because of their high toxicity towards microorganisms and nematodes. From the available data, it appears that the 5,6-di-(middle halo) and the 2,5,6 tri(middle halo) compounds of this subclass have the highest toxicity towards a broad spectrum of organisms.

Examples of specific compounds encompassed by the present invention follow.

2,5 ,6-trichloro-1-a,2,3 ,3a-tetrahydro-3 a-ethoxy 1,3-

methano-1H-cyclopropa(cd) naphthalene-4,7-dione 2,5 or 6)-dichloro-1a,2,3,3a-tetrahydro-3a,6 (or 5) diethoxy-1,3-methano-1H-cyclopropa(cd) naphthalene-4,7-dione 3,291,835 Patented Dec. 13, 1966 2,5 ,6-trichloro-l21,253,3a-tetrahydro-3a-methoxy-1,3-

2,5,6-trichloro-1a,2,3,3a-tetrahydro3 a- (2-hydroxyethoxy) 1,3 -methano-1H-cyclo propa(cd) naphthalene-4,7-dione 2,5 ,6-trichloro-l-a,2,3 ,3 a-te-trahydro-3 a-( 2,3-

dihy droxypropoxy) -1,3-methano-1H-cyclopropacd naphthalene-4,7-dione 2,5,6 -trichloro-1a,2,3 ,3a-tetrahydro-3 a- (dibromoethoxy) -1,3 -methano-1H-cyc1opropa (cd) naphthalene- 4,7-dione 2,5,6-trichlorol a,2,3 ,3 a-tetrahydro-3 adichloroethoxy) -1,3 methano-1H-cycl0propa(cd) naphthalene- 4,7-dione 2,5,6-trich1oro-1a,2,3,3 a-tetrahydro-3 a-(1,2-dibromoprop oxy) 1 ,3-rnethano- 1 H-cyclopropa (cd) n aphth alene-4,7-dione 2,5 ,6-trichloro-l a,2,3 ,3 a-tetrahydro-3 a-(tetrahydrofurfuryloxy) -1,3-methano-1H-cyclopropa(cd) naphthalene-4,7-dione 2,5,6-trichloro-1a,2,3 ,3 a-tetrahydro-3 a-(-tetrahydropyran-Z-ylmeth-oxy) -1, 3 -methano-1H-cycloprop acd naphthalene-4,7-dione 2,5,6-trichloro-1a,2,3,3 a-tetrahy-dro-3a-(2,2-dimethyl- 1,3 -dioxolan-4-ylmethoxy) -1,3 -methano-lH-cyclopropa (cd) naphthalene-4,7-dione The novel compounds of the present invention may be made by alcoholysis of halogen-substituted polyhydro-l,4-methanonaphthalene-5,8diones having halogen substituted on at least one of the carbon atoms of the 1,4-ethano bridge (that is, on at least one of the carbon atoms in the 2- and 3-positions) and having a double bond, actual or potential (by virtue of readily removable substituent groups or atoms), in the homoallylic (4a, 8a) position. The most valuable compounds of the invention have been prepared from such halogen-substituted polyhydro-l,4-methanonaphthalene-5,S-diones that are substituted by chlorine at least in both the 2- and 3- or both the 2- and 9-positions of the nucleus. Particularly valuable as starting materials are the tetrahydroand the hexahydro-l,4-methanonaphthalene 5,8 diones that are thus substituted by chlorine.

Of particular interest as starting materials are the 2,6, 7,9 tetrahalc 1,2,3,4 tetrahydro 1,4 methanonaph-thalene-5,8-diones such as 2,6,7,9-tetrachloro-1,2,3,4- tetrahyclro 1,4 methanonaphthalene 5,8 dione and 2,4a,6,7,8a,9 hexahalo 1,2,3,4,4a,-8a hexahydro 1,4- methanonaphthalene-S,S-diones such as 2,4a,6,7,8a,9-hexa chloro 1,2,3,4,4a,8a hexahydro 1,4 methanonaphthalene-5,8-dione.

The alcoholysis of these halogen-substituted polyhydro- 1,4-methanonaphthalene-5,8-diones leads to the removal of a halogen atom from the 1,4-ethano bridge, to formation by homoallylic displacement of a cyclopropane ring that includes one of the ring carbon atoms to which the methano bridge is bonded, and to introduction of the group RO- (R' being as defined he'reinbefore) onto one of the two carbon atoms that are common to the fused bycycloheptane (or -ene) and hexatomic quinoid rings of the parent halogen-substituted polyhydro-l,4-methanonaphthalene-5,8-dione. For accomplishing the alcoholysis there may be employed an alcohol ROH, corresponding to the group RO- that it is desired to introduce, in conjunction with an alkaline acting or other known alcoholysi-s agent, or there may be employed a reagent which serves both as the source of the RO group and as the catalyst.

The choice of the alcohol, R'OH, will depend upon the substituent group RO that will be present in the desired product. Illustrative alcohols which may be used include, among others, methyl alcohol, ethyl alcohol, propyl alcohol, isopropyl alcohol, the butyl alcohols, allyl alcohol, and higher aliphatic alcohols containing up to ten or even more carbon atoms; methoxyethyl alcohol, hydroxyethyl alcohol, dihydroxy-propyl alcohol, tetrahy drofurfuryl alcohol, tetrahydropyranyl alcohol and benzyl alcohol.

Alkaline acting materials which may be used as agents for the alcoholysis include such inorganic alkaline-reacting materials as the oxides, hydroxides, and carbonates of the alkali metals (including ammonium) and of the alkaline earth metals, for example, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium carbonate, ammonium hydroxide, ammonium carbonate, sodium bicarbonate, calcium oxide, barium hydroxide, and the like. Organic bases, such as amines and amine salts and quarternary ammonium bases, including triamyl amine, ethanolamine, triethanolamine, triamyl amine phosphate, benzyltrimethylammoni-um hydroxide, and the like, may also be employed. Other known alcoholy-sis agents which may be used include, for example, metals that are capable of replacing hydrogen from the hydrohalic acids, e.g., zinc, magnesium, iron, etc., preferably employed in finely divided state, e.g., zinc dust, iron filings, brass spelter, or the like. Zinc has been found to be an especially efliective agent, both as the sole agent and used in conjunction with one or more alkaline acting materials as described hereinabove.

Instead of reacting the parent halogen-substituted polyhydro-l,4-methanonaphthalene-5,8- dione with an alcohol in the presence of a separate alcoholysis agent, the alcoholysis may also be conducted by treatment of the parent halogen-substituted polyhydro-l,4 methanonaphthalene-5,8-dione with an alkoxide of an alkali metal, of an alkaline earth metal, or of an earth metal, corresponding to the group RO that it is desired to introduce, such as sodium ethoxi-de, potassium methoxide, magnesium ethoxide, aluminum triisopropoxide, aluminum phenoxide, etc.

The aleohollysis step (that concomitantly leads to formation of the cyclopropane ring, as discussed hereinbefore) of the process of the present invention may be conducted by heating together the parent halogen-substituted polyhydro-l,4-methanonaphthalene-5,8-d-ione, the alkaline acting material in sufficient quantity to neutralize liberated hydrohalic acid, and the alcohol in at least the stoichiometric amount. Where an alkoxide is used as both the sour-cc of the RO group and as the alkaline acting material, the amount of the alkoxide will, of course, be determined on the basis of stoichiometry. A convenient method of conducting the reaction is to heat the reactants together at reflux in the presence of a solvent, which may be an inert solvent such as benzene, xylene, toluene, hep-tame, decane, or other saturated or aromatic hydrocarbon solvent, or may, even more simply, be the alcohol itself present in excess over the amount required for the reaction. Reaction temperatures within the range of from about room temperatures up to about 200 C., preferably up to about C., may be employed, although these are not critical and the optimum temperature will depend upon the particular reactants that are involved. After completion of the reaction, the product can be recovered by conventional methods, e.g., from crystallization from solvents, extraction, etc. The products of the invention are, in general, high-melting solids that, owing to the likelihood of decomposition, are not amenable to distillation.

In schematic terms, compounds of this invention can be prepared by the following routes (R and R have the respective meanings already given and R =R, the subscript being used for clarity):

A. (H) E) R AR l l l R0 R R R 0 )K (I) +HX (x 'ddl hl X pred ably chl o i r i (J R R H o l (H) base E (III) 0 X \A (III) (oxidation) 1 1 c) (IV) i l\/\ (1V) R'OH mild base i Re R I 01 n G I 01 \/\C1 l I I l R c1 or R G1 II 01 0 0 (v1 0 01 H X \A (v1 11x I R or 01 (VII) metal (Zn, Fe) 3/01} i R or /\H/ 0 (VIII) (VIII) ROH mild base g (IX) R! II O-alkyl (IX) MO-alkyl (M=alkali metal) I 0 0 (X) R I I Oolkyl (IX) 2MO-alky1 R O-alkyl O 0 (X1 RI D. I I

A R n I tr R R R \H/ H 0 0 (XII) X R (XII) RDOH hypohalite (x=halogen) (XIII) (XIII) base OH (XIV) X R (XIV) (oxidation) R00 R I? L v) R'oH mild base R0O\ \\/R O C (XVI) R! (XVII) oxidation (chromic acid) (XVIII) i 5 X 01 (XVIII) ROH mild base 0 0 (XIX) R! By way of example, one complete sequence of steps for the production of compounds of the present invention follows. It should be understood that though the following sequence of steps shows the preparation of 2,5,6 trichloro 1a,2,3,3a tetrahydro 3a ethoxy 1,3-

Inethano-1H-cyclopropa(cd)naphthalene 4,7 dione it also applies to other compounds of the present invention which diifer only in the substituents on the ring.

J 1 basic catalyst J solvent ll 0 OH 1,4,4a,8a-tetrahydro-1,4- 1,4-dihydr0-L4-methanomethanonaphthalene-5,8- naphthalene-5,8-diol dione A12 l C1: I!

0 0 Vi 01 c1 01 o1 l I H 01 01 II 0 0 2,6,7,9-tetraehloro-1,2,3,4- 2,4a,6,7,8a,Q-hexachlorotetrahydro-l,4-methano- 1,2,3,4,4a,8a'hexahydronaphthaleue-5,8-dione 1,4-methanonaphthalene- 4O 5,8-dione CZHEOH Zn \mild +EtoH base /+Na.HO 03 \I I! An alternative method for the production of this compound follows:

l acetic anhydride I sodium acetate I I I Oyclopeutadlene- 6O p-benzoquinone adduct O I] ll 2,5,6-trichloro-1a,2,3,3a-tetra hydro-3a-ethoxy-L3-methanolH-cyclopropa (ed)- naphthalene-4,7-di0ne CzHsOH NaHC O;

2,6,7,9-tetra.chloro1,2,3,4-tetrahydro-l,4-methanonaphthalene- 5,8-dione 1,4-dihydro-1,4-methano- 2,6,7,9-tetraehloro-l,2,3,+ naphthalene-5,8-diol tetrahydro-l,4-methanonaphthalene-5,8-diol or MES O3 01 01 n i o H 0H 01- i c1 01 2 5 01 Y n ozrno 0 o 2,5,6-trichloro-1a,2,3,3a-

tetrahydro-iiarethoxy-l ,3- methano-lH-eyclopropa(cd)- na hthalene-4,7-dione 2,6,7,9-tetrachlor0-1,2,3,4-

tetrahydro-lA-methanonaphthalene-5,8-dione Another method for the preparation of compounds of the present invention employing the cyclopentadienechloraniil adduct follows:

OGOOH;

1,4-dihydro-1,4-methanonaphthalene-5,8-diol diacetate O G O CH;

2,6,7,9-tetrachloro-l,2,3,4 tetrahydro- O G O 0 H 1,4-methanonaphthalene-5,8-dio1 diacetate Employing the diol diaceta-te so produced, 2,5,6-trichloro-1a,2,3,3a-tetrahydro 3a ethoxy 1,3 methanolH cyclopropa(cd)naphthalene 4,7 dione may he made in accordance with methods already described. Other compounds of the present invention may also be made in accordance with the described method employing the cyclopentadienechloranil adduct.

Another preparation of compounds of the present invention as exemplified -by 2,5,6 trichloro la,2,3,3a tetrahydro 3a erthoxy 1,3 methano lH cyclop-ropa- (cd)naphthalene 4,7 dione follows. In this instance, the product is a stereoisomer of the compound prepared in accordance with methods already described. Those versed in the art will recognize that four isomers of this dione are possible.

l G1 a GI "01 Cl 01 V01 cyclopentadiene 2,3,4a,6,7,8a-hexachlorochloranil adduet 1,2,3,4,4a,8a-hexahydro-1,- 4-methan0naphthalene-5,-

dione Zn Zn OH5OH NaHC 0 1,2,3,4-tetrahydro- 1,4-methanonaphthalene- 5,8-dione The 1,4-methano 1H cyclopropa(cd)naphthalene 5,8 dione obtained by synthesis firom the cyclopentadiene-chloranil adduct is a stereoisomer of the product obtained by synthesis from the cyclopentadiene p ibenzoquinone adduct. The principle upon which the difference between these compounds is based can be gleaned from a consideration of the basic nortricyclene structure present in the compounds of this invention. This discussion ignores isomer pairs which are possible by virtue of one being the mirror image of the other; these are the well-known dl pairs of optical isomers.

In nortricyclene a system exists which contains a cyclopropane ring each of whose carbon atoms is connected to a common carbon atom through a methylene bridge. This arrangement of seven carbon atoms provides a system having a three-fold axis of symmetry which is to be seen in its three planes of symmetry each defined by the common carbon atom, one methylene carbon and the carbon atom of the cyclopropane ring to which the latter is joined. By virtue of this symmetry all three methylene carbons are geometrically equivalent and the external bonds of a methylene group are likewise equiv alent. A consequence of these relationships is that a nortri-cyclene having one of its methylene carbons with a single substituent or even two difierent substituents exists in but one geometric form. It will be immediately recognized that when this system bears two substituents on different methylene carbons a number of different geometric forms can exist.

The novel 1,3 methano-lH cyclopropa(cd)naphthalene-5,8-diones of this invention have a cyclohexenedione unit fused with a nortricyclene unit as shown in the following illustrations for IV.

hy(ire-3a-ethoxy-1,3-methano-1H- tgl clopropamd)naphthalene-4,7-

one

It can be seen in this system that carbon atom 3a when considered as part of the nortricyclene unit has one of its external bonds as part of the cyclohexenedione ring structure. Since the enedione portion of the molecule is symmetrical and the bond between carbon atoms 7a and 7 is the only possible external bond for the nortricyclene unit at that point, no new elements of geometry are introduced by these structural units. Thus, on the basis of the reasoning presented above for nortricyclene, only one geometric form is possible for 1a,2,3,3a-tetrahydro-1,3- methano-lH-cyclopropa(:cd)naphthalene-4,7-dione IV, as well as for the case where position 3a of IV is substituted, as by ethoxyl.

When, however, the structure represented by IV bears in addition to an ethoxyl group at position 3a a chlorine atom at position 2 or 8, then four geometric forms are evident. These four isomers can be understood when the chlorine atom is positioned at orientation 0, a, e, or f of IV. Each of these external bonds of carbon atoms 2 and 8 is recognized as being differently oriented when viewed against the two unlike substitutions in.the nortricyclene unit at position 30.

The distinguishing features of these orientations can also be recognized in considering the terminology cistrans and syn-anti which can be employed. With bond 311-4 as a reference point, orientation is cis when considering the geometry of the bonding of these two bonds to their common cyclopentane ring, in this case 1a, 2, 3, 3a, 7a. Then taking the plane defined by atoms 3, 3a and 7a as a point of reference, it can be seen that orientation c is on the same side of the plane as bond 3a-4. Thus, 0 is completely designated as cis-syn. Using these two frames of reference, the designations become for a, trans-syn; for e, cis-anti; for f, trans-anti.

These symbolisms become especially valuable in differentiating by name the four isomers, say of 2,5,6-trichloro- 1a,2,3,3a tetrahydro-3a ethoxy-1,3 methano-1H-cyclopropa(cd)naphthalene. It is recognized that in this composition the chlorine atoms :at positions 5 and 6 are symmetrically placed and thus do not produce new geometric forms. Thus, the chlorine at position 2 can be assigned any one of the four spatial orientations mentioned above. Although in the perspective drawing of IV positions 2 and 8 appear unlike, the difference no longer exists in a nonperspective representation of the molecule, the two methylene groups of IV appearing equivalent as they do in nortricyclene. Since the naming of compounds following the practice of Chemical Abstracts requires the assigning of the lowest number to a substituent and only nonperspective representations are considered, position 2 is used for the third chlorine. Then, with the four symbolisms a complete name can be given to any one of the isomers.

It is believed that the principal product of the method, starting with the cyclopentadiene (p-benzoquinone) adduct, can be represented non-perspectively by having its chlorine in the 2-position oriented cis-anti and that where the cyclopentadiene chloranil adduct is employed the similar chlorine is oriented trans-syn. It is also believed that the crude products of the two methods also contain varying amounts of the other isomers involving the orientation of the chlorine at position 2.

The invention can be best illustrated by the following examples which demonstrate the various embodiments.

EXAMPLE I 2,5 ,6-trich loro-Z a,2,3,3 a-zetrahydr0-3a-eth0xy-I ,3 methano-1 H -cycl0propa( ca naphthalene-4,7-di0ne 9.36 grams of 2,6,7,9-tetrachloro-1,2,3,4-tetrahydro-1,4- methanonaphthalene-S,8-dione, 2.52 grams of sodium bicarbonate, 14 milliliters of benzene, and 33 milliliters of absolute ethanol were refluxed with stirring for six hours. The reaction mixture was filtered to remove the inorganic material. The filtrate was evaporated and filtered to give 6.4 grams of 2,5,6-trichloro-1a,2,3,3a tetrahydro- 3aethoxy- 1,3 methano 1Hcyclopropa(cd)naphthalene- 4,7-dione, melting point, 172l73 C.

Analysis-Calculated for C H Cl O Percent C1,

10 48.6; percent C, 33.0; percent H, 3.4. Found: Percent Cl, 48.6; percent C, 32. 6; percent H, 3.6.

In the same manner, 2,5,6-trichloro-1a,2,3,3a-tetrahydro-3a hexyloxy-l,3 methano-1H- cyclopropa(cd) naphthalene-4,7-dione, melting point 48-49 C., was prepared substituting forthe ethanol an equivalent amount of n-hex-yl alcohol.

Analysis-Calculated for C H Cl O Percent Cl, 28.2; percent C, 54.1; percent H, 5.0. Found: Percent Cl, 28.0; percent C, 54.2; percent H, 5.2.

EXAMPLE II 78 grams of 2,6,7,9-tetrachloro-1,2,3,4-tetrahydro-1,4- methanonaphthalene-S,8-dione was suspended in 960 milliliters of absolute ethanol and 8 grams of zinc dust was added. The mixture was refluxed for three hours, filtered and allowed to stand overnight. The precipitate which formed was removed by filtration and was crystallized from methanol. The product analyzed as 2,5,6- trichloro-la,2,3,3a tetrahydro-3a ethoxy-1,3-'methano- 1H-cyclopropa(cd)naphthalene-4,7-dione, melting point 169-171" C., amount 20 grams.

EXAMPLE III EXAMPLE IV 5.5 grams of 2,6,7,9-tetrachloro-1,2,3,4-tetrahydro-l,4- methanonaphthalene-S,8-dione was dissolved in milliliters of boiling absolute ethanol and 3 grams of aluminum ethoxide was added. The mixture was refluxed for 30 minutes, filtered and evaporated to a small volume. Water was added and the product was extracted with benzene. The benzene extract was evaporated to near dryness and the residue was triturated with hexane to give the desired product as a precipitate which weighed one gram, melting point 169-171 C.

EXAMPLE V 4.7 grams of 2,6,7,9-tetrachloro-1,2,3,4-tetrahydro-1,4- methanonaphthalene-5,8-dione was refluxed in 25 milliliters of benzene and 25 milliliters of ethanol with one gram of Mg(OC H for 7 hours. The reaction mixture was filtered and the filtrate was evaporated to a small volume, chilled and filtered to give 1.9 grams of 2,5,6- trichloro-1a,2,3,3a-tetrahydro-3a-ethoxy-1,3-methano-1H- cyclopropa(cd)-4,7-dione, melting point 166169 C.

EXAMPLE VI 4.7 grams 2,6,7,9 tetrachloro 1,2,3,4-tetrahydro-1,4- methanonaphthalene-S,8-dione and 0.72 gram of were refluxed in 30 milliliters of benzene and 70 milliliters of absolute ethanol for 20 hours. The reaction mixture was evaporated to a small volume and filtered to give 2.4 grams of 2,5,6-trichloro-1a,2,3,3a-tetrahydro-3aethoxy-1,3-methano-1H-cyclopropa(cd)naphthalene 4,7- dione, melting point 163-166 C.

EXAMPLE VII 4.7 grams of 2,6,7,9-tetrachloro-1,2,3,4-tetrahydro-1,4- methanonaphthalene-S,8-dione was dissolved in 50 milliliters of benzene and a solution of sodium hydroxide in ethanol (0.6 gram NaOH in 50 milliliters C H OH) was added in 30 minutes with vigorous stirring. The mixture was allowed to stand for another 30 minutes and filtered to remove the inorganic sodium chloride. The filtrate was evaporated to a small volume, filtered to give 2.75 grams 2,5,6-trichloro-1a,2,3,3a-tetrahydro-3a-ethoxy 1,3- methano-lH-cyclopropa(cd)naphthalene-4,7-dione.

EXAMPLE VIII (ed)naphthalene-4,7-dione, melting point 166169 C.

EXAMPLE IX 5.0 grams of 2,4a,6,7,8a,9 hexachloro 1,2,3,4,4a,8ahexahydro-1,4 methanonaphthalene 5,8 dione was refiuxed with 2.05 grams of zinc dust in 100 milliliters of absolute ethanol for 3 hours. A gradual change of color to orange and then to brown was apparent. The reaction mixture was filtered to remove zinc. The filtrate was then shaken with water and an amorphous brown solid was separated. The solid which was insoluble in hexane, but very soluble in benzene or methanol, was then extracted with carbon tetrachloride, yielding a dark red solution and an insoluble dark residue, which was discarded. The dark red solution was evaporated to a small volume and cooled, and an amorphous brown solid which separated was discarded. The filtrate was evaporated to dryness and the residue was dissolved in methyl alcohol and cooled. Two-tenths gram of yellow crystals, melting point 148158 C., was obtained. These crystals were recrystallized from ethyl alcohol, yielding the desired product having a melting point of 164166 C.

EXAMPLE X 38.3 grams of 2,4a,6,7,8a,9-heXachloro-1,2,3,4,4a,8ahexahydro-l,4-methanonaphthalene-5,8-dione was mixed with 6.3 grams of zinc, 9 grams of sodium bicarbonate, 80 milliliters ethanol and 40 milliliters of benzene. The mixture was then refluxed for 4 hours and the inorganic material was filtered. The filtrate was concentrated to a small volume to give 10 grams of a tan solid having a yellowish tint, melting point 161-167 C., mixed melting point with 2,5,6-trichloro-1a,2,3,3a-tetrahydro-Sa-ethoxy- 1,3-methan0-1H-cyclopropa(cd)naphthalene 4,7 dione, 163-169 C. This product was recrystallized from benzene to give 8 grams of pure product as a light yellow material, melting point 170l72 C.

In the preceding examples, the difierences in melting points of the respective products are attributable to difien ences in purity. Pure 2,5,6-trichl0ro-1a,2,3,3a-tetrahydo-3a-ethoxy-1,3-methano 1H cyclopropa(cd)naphthalene-4,7-dione melts at approximately 172-3" C. as illustrated by the preparation described in Example I.

EXAMPLE XI 2,5,6-trichloro-1a,2,3,3a-tetrahydro-Sa-ethoxy 1,3 methan0-1H-cycl0propa(cd)naphthalene-4,7 dione (isomer of the compound of Examples I through X) 15.6 grams of the adduct of cyclopentadiene and chloranil was suspended in 50 milliliters of CH Cl and a stream of chlorine gas was introduced. No evolution of heat was observed. A few iodine crystals were then added to the mixture. An exothermic reaction was observed. The chlorination was continued until no heat was evolved. The reaction mixture was filtered and the solid was washed with CH Cl to give a yellow precipitate which was chloranil, weight 1.2 grams. The filtrate Was evaporated to dryness and the residue was treated with hexane and filtered to give a tan precipitate which melted at 147154 C. and depressed the melting point of the starting material. This material was again chlorinated in 50 milliliters of CH Cl in the presence of iodine for half an hour. The reaction mixture was evaporated to dryness and triturated with hexane to give a light tan solid, melting point 161-165 C., weight 12.5 grams. This product was recrystallized from ethyl acetate to give the product as a light yellow solid melting at 170171 C., weight 7.0 grams (A). Second crop: 4.2 grams, melt ing point 164-167" C. (B). Crop (A) was analyzed.

Analysis-Calculated for C H Cl O z Cl, 55.3; C, 34.5; H, 1.6. Found: Cl, 55.2; C 34.4; H 1.6.

5.0 grams of the above-described product (4.2 grams of (B) and 0.8 gram of (A)) were mixed with 0.85 gram of zinc and milliliters of absolute ethanol. The mixture was refluxed with stirring for 4 /2 hours and filtered to remove unreacted zinc. The filtrate was concentrated to yield 1.8 grams of product as a yellow solid, melting point 200-202" C.

Analysis.Calculated for C H Cl O Cl, 45.5; C, 42.3; H, 1.9. Pound: Cl, 45.5; C, 41.8; H, 2.2.

1.3 grams of the above tetrachloroquinone was refluxed with 0.42 gram NaHCO in 40 milliliters of ethanol for 6 hours and the mixture was filtered to remove the inorganic material. The filtrate was evaporated to small volume to give 1.1 grams of light yellow product, melting point 177-179 C. It was recrystallized from ethyl acetate to give a crystalline product, M.P. 180-1 C.

Analysis.Calculated for C H Cl O Cl, 33.1. Found: Cl, 33.1.

EXAMPLE XII 2,5,6 Trichloro 1a,2,3,3a tetrahydro 3a-ethoxy-1,3-

methano 1H cyclopropa(cd) naphthalene 4,7-di0ne (isomer of the compound of Examples I through X) Methods of preparation of 2,'3,6,7-tetrachloro-1,2,3,4- tetrahydo-1,4-methanonaphthalene-5,8-dione by chlorination of 6,7-dichloro-1,4-dihydro-1,4-methanonaphthalene- 5,8-dione.

(1) 355 grams of gaseous chlorine was added to a solution of 964 grams of 6,7 dichloro 1,4 dihydro 1,4- methanonaphthalene-S,8-dione in 4800 milliliters methylene chloride over a period of 1 /2 hours with constant stirring. The exothermic reaction brought the reaction mixture to boiling. After the addition of chlorine the reaction mixture was evaporated to a smaller volume, chilled, filtered and washed with methanol to give 655 grams of yellow solid, melting point, 230-4 C. It was recrystallized from ethyl acetate to give yellow crystalline 2,3,6,7 tet-rachloro 1,2,3,4 tetrahydro 1,4 methanonaphthalene-5,8-dione melting at 236'.57 C.

Analysis.Calculated for C H O Cl C, 42.3; H, 1.9; CI, 45.5. Found: C, 42.7; H, 2.0; CI, 45.3.

A suspension of 468 grams of this isomer of 2,3,6]- tetrachloro 1,2,3,4-tetrahydro-1,4-methanonaphthalene- 5,8-dione and 126 grams of sodium bicarbonate in 4500 milliliters of absolute alcohol was refluxed for 24 hours. The reaction mixture was filtered While hot to remove the inorganic salt which gave a positive test for chloride and negative test for carbonate. The filtrate was evaporated to a smaller volume, chilled, filtered and washed several times with methanol to give 238 grams of a solid melting at -172. Its was recrystallized from ethyl acetate and then from benzene to yield 2,5,6-trichloro-1a,2,3,3a-tetrahydro 3a ethoxy 1,3 methano 1H cyclopropa(cd) naphthalene-4,7-dione, as a light yellow crystalline solid, melting point, 174.5- C. The identity of the product was confirmed by elemental analysis:

Analysis-Calculated for C H O Cl C, 48.5;

% H, 3.4; Cl, 33.1. Found: C, 48.3; H, 3.6; CI, 33.2.

EXAMPLE XIII 2,5(01' 6)-Dichl0r0-1(1,2,3,3a-tetrahydr0-3a,6(0r )-diethoxy 1,3 methan0-1H-cycl0pr0pa(cd)naphthalene- 4,7-di0ne 0 ll I 9.36 grams of 2,6,7,9-tetrachloro-1,2,3,4-tetrahydro- 1,4-methanonaphthalene-5,8-dione was dissolved in 200 milliliters of boiling absolute ethanol and a solution of sodium ethoxide, prepared by dissolving 1.38 grams of sodium in 50 milliliters of ethanol, was added dropwise with stirring in about half an hour. A precipitate of sodium chloride which formed immediately was filtered. The filtrate was evaporated to a small volume to give two crops: Crop A, 3.2 grams, melting point 108-118", and Crop B, 0.7 grams, melting point 108-114". Crop A was recrystallized from methanol to give 2.6 grams of product, melting point 112-114", which was analyzed.

Analysis.Calculated for C H Cl O Cl, 21.5. Found: Cl, 21.6.

EXAMPLE XIV 2,5,6 triclzloro ]a,2,3,3a tetrahydro 3a-meth0xy-1,3- methano-l H -cycl0proprz(cd naphthalene-4,7 -di0ne 9.3 grams of purified 2,6,7,9-tetrachloro-1,2,3,4-tetrahydro-1,4-methanonaphthalene-5,8-dione was dissolved in 200 milliliters of boiling methanol and a solution of sodium methoxide in methanol was added with stirring in about 20 minutes. The resulting mixture was evaporated and the precipitate was filtered and washed with water and methanol to give 3.1 grams of products, melting point 148-153 C., which was recrystallized from methanol several times to yield 2.7 grams of light yellow product, melting point 158-159 C.

Analysis-Calculated: chlorine, 34.6; methoxyl, 10.1. Found: chlorine, 33.8; methoxyl, 9.6.

EXAMPLE XV 2,5,6 trichloro 1a,2,3,3a tetrahydro 3a pr0poxy-1,3-

methan0-1H-cycl0pr0pa(cd )naphthalene-4,7-di0ne 9.3 grams of purified 2,6,7,9-tetrachloro-1,2,3,4-tetrahydro-1,4-methanonaphthalene-5,S-dione was dissolved in 100 milliliters of benzene and .a solution of sodium propoxide was added dropwise with stirring in one hour. The reaction mixture was filtered to remove 1.55 grams of sodium chloride and the filtrate was concentrated to remove all benzene and chilled to give a gummy precipitate. Addition of methanol to the precipitate yielded a light yellow material, melting point 95-98 C., weight 4.45 grams. This product was recrystallized from methanol, yielding 3.5 grams of crystalline product, melting point 100-101 C.

Analysis.Calculated for C H CI O Cl, 31.8. Found: Cl, 31.3.

EXAMPLE XVI 2,5,6 trichloro 1a,2,3,3a-tetrahydro-Sa-methoxyethoxy- I,3-methan0-1H-cyclopropa(cd naphthalene-4,7-di0ne 31.2 grams of 2,6,7,9-tetrachloro-1,2,3,4-tetrahydro-1,4- methanonaphthalene-S,8-dione was heated on a steam bath in 75 milliliters of methyl cellosolve and a solution of 4.8 grams of (NH )CO in 50 milliliters water was added. The reaction mixture was heated for one-half hour and diluted with water. The gummy precipitate obtained was washed with water and dissolved in boiling methanol. Three crops were obtained. The first crop melted at 175-180 C. and weighed 5.5 grams. The second crop melted at 90 C. and weighed 11 grams, and the third crop melted at -110 C. and Weighed one gram. The residue was discarded. The second crop was recrystallized from methanol to give 6 grams of light yellow material, melting point 91-96 C., which was chromatographed through a column of activated alumina in CH Cl to give four grams of light yellow crystalline product, melting point 95.5-96.5 C.

Analysis.Calculated for C H CI O Cl, 30.3; C, 47.8; H, 3.7. Found: Cl, 30.5; C, 47.5; H, 3.7. I

EXAMPLE XVII 2,5,6 trichloro 1a,2,3,3a-tetrahydr0-3a-'(chlo roethovcy)- 1 ,3-methano-1H-cycl0pr0pa (cd) ndphthalene-4,7-dione 31.2 grams of 2,6,7,9-tetrachloro-1,2,3,4-tetrahydro-1,4- methanonaphthalene-S,8-dione and 8.4 grams NaHCO were suspended in 50 milliliters benzene and 100 milliliters ClCH CH OH. The mixture was refluxed for 5 hours at 92 C. with stirring. The solvent was stripped to about one-third its original volume and washed with water. The gummy residue was triturated with MeOH and allowed to stand. A solid was formed which was filtered and washed with MeOH to give 14 grams of light yellow material, melting point 134-137" C. This product was recrystallized from benzene to give solid product, melting point 136-137 C.

Analysis.-Calculated for C H 'O Cl CI, 39.9; C, 43.8; H, 2.8. Found: Cl, 40.2; C, 44.0; H, 3.0.

- EXAMPLE XVIII 2,5,6, trichloro 1a,2,3,3a tetrahydro 3a allyloxy-I,3- methan0-1H-cycl0pr0pa(cd)naphthalene-4,7-di0ne 62.4 grams of 2,6,7,9 tetrachloro-1,2,3,4 tetrahydro- 1,4-methanonaphthalene 5,8 dione was mixed with 17.6 grams NaHCO in 100 milliliters benzene and 50 milliliters of allyl alcohol and then refluxed for 3 hours. The reaction mixture was filtered to remove the inorganic salt and the filtrate was evaporated to dryness and the residue was triturated with MeOH to give a yellow precipitate which was recrystallized from MeOH to give 12 grams of light yellow product, melting point -1268.

Analysis.-Calculated for C H O Cl Cl, 31.9; C, 50.4; H, 3.3. Found: Cl, 30.7; C, 49.7; H, 3.3.

EXAMPLE XIX 2,5 ,6-trich loro-J a, 2,3,3 a-tetrahydr0-3a-benzy loxy-I ,3 methano-I H -cycl0pr0 pa'(cd naph thalene-4, 7 -di0ne A mixture of 35 grams of 2,6,7,9-tetrachloro-1,2,3,4- tetrahydro-1,4-methan-onaphthalene-5,8-dione, 8.4 grams of sodium bicarbonate, 5'0 milliliters of benzyl alcohol and 75 milliliters of benzene was stirred at reflux for 15 hours. The mixture was filtered and the inorganic salt was washed with methylene chloride. The filtrate was concentrated in vacuum and the residue was taken up in methylene chloride and chromatographed twice on alumina. Concentrating the eluent left a brown symp which was steam distilled. The residue was extracted with boiling hexane and then concentrated to give an orange oil which crystallized from cold methanol to give 8 grams (21% yield) of 2,5,6-trichloro-1a,-2,3,3a tetrahydro-3abenzyloxy 1,3-methano-1H-cyclopropa(cd)naphthalene- 4,7-dione, melting point 128-129" C.

Analysis.Calculated for C H Cl O Cl, 27.8; C, 56.4; H, 3.4. Found: Cl, 27.1; C, 56.6; H, 3.3.

1 5 EXAMPLE XX 2,5,6 trichloro 1a,2,3,3a tetrahydro 3a (tetrahydrofurfuryloxy) 1,3 methano 1H cyclopropa1(cd) naphthalene-4,7-dione A mixture of 312 grams of 2,6,7,9-tetrac'hloro-1,2,31,4- tetrahydro-1,4-methanonaphthalene-5,8-dione, 92 grams of sodium bicarbonate and 306 grams of tetrahydrof-urfuryl alcohol in 300 milliliters of benzene was heated at 90 C. for 8 hours with stirring. The reaction mixture was poured into'water and extracted with ether. The ether extracts were combined and concentrated under vacuum to give a dark brown viscous liquid. This liquid was chromatographed in methylene chloride through a column of silica gel and then a column of activated alumina. The eluate was evaporated to dryness under vacuum to give 263 grams of a viscous syrup. This syrup was crystallized from methanol to give a 2,5,6-trichloro- 1a, 2,3,3a-tetrahydro 3a (tetrahydrotfurfuryloxy-l,3- methano 1H cyclop=ropa(cd)naphthalene 4,7-dione as a solid which melted at 50 C.

Analysis.Calculated f]: C H C1 O Cl, 28.2. Found: Cl, 28.2.

EXAMPLE XXI 2,5,6 trichloro-Ia,2,3,3a-tretrahydr0-3a-hexyloxy 1,3- methano-iH-cyclopropflcd)naphthalene-4,7-dione A suspension of 15.6 grams of 2,3,6,7 tetrachloro- 1,2,3,4 tetrahydro 1,4 methanonaphthalene-5,8-dione, isomer melting at 236.5-70" C., and 4.2 grams of sodium bicarbonate in 50 milliliters of n-hexyl alcohol were heated at 100-105 C. with stirring for 22 hours. The reaction mixture was filtered while hot to remove inorganic salt which gave a positive test for chloride and negative test for carbonate. The filtrate was evaporated to dryness under vacuum to leave .a gummy residue. It was chromatographed in methylene chloride through a column of activated alumina. After removal of methylene chloride 2,5, 6-trichloro-1la,2,3,3.a-tetrahydro-3ahexyloxy-1,3-methano-1H-cyclopropa(cd)naphthalene 4,7 dione, was obtflllllfid as a waxy solid: weight 7. 6 grams.

. Analysis.--Calculated for C I-1 G 0 C, 54.0; H, 5.0; Cl,28.2. Found: C, 53.8; H, 5.2; C1, 28.1.

EXAMPLE XXII 2,3,6, 7-tetrach lore-1 ,2,3 ,4-tetrahydro-I ,4 -methanonaphthalene-5,8-dione A suspension of 624 grams of 4a,6,7,8a-tetrachloro- 1,4,4a,8a-tetr-ahydro 1,4 methanonaphthalene 5,8- dione and 4 grams of iodine in 1250 milliliters of chloroform was treated in 7 hours with 265 grams of chlorine gas. The reaction mixture was heated over a steam bath to remove the excess chlorine, chilled and filtered to give 297 grams of solid, melting point 165-7 The filtrate was evaporated to near dryness and the resulting solid was triturated with hexane, filtered and Washed with ethyl acetate to :give a second crop, 178 grams, melting point 164-6". Recrystallation from ethyl acetate gave light yellow crystalline 2,3,4a,6,7,8ahexachloro 1,2,3,4,4a,8ahexahydr-o-1,4methanonaphthalene-5,8-dione melting at 170- 1 C.

Analysis.Calculated for C H Cl O t 01, 55.3; C, 34.4; H, 1.6. Found: CI, 55.2; C, 34.5; H, 1.6.

A suspension of 11.49 grams of 2,3,4a,6,7,8a-hexachloro 1,2,3,4,4a,8a-hexahydro 1,4 methanonaphth- -alene-',8-dione melting at 170-1 C. and 1.94 grams of powdered iron in 50 milliliters of absolute alcohol and 30 milliliters of benzene was refluxed for 24 hours with stirring. The reaction mixture was evaporated to dryness and the residue was extracted several times with boiling benzene. The benzene extract was evaporated to a small volume to give two crops of yellow product. The first crop weighed 3.5 grams and melted at 200-2 C.

and the second crop weighed 1.65 grams and melted at EXAMPLE XXIII 2,3 ,6, 7-tetrachZ0r0-1 ,2,3 ,4 -tetrahydr0-I ,4-methan0- naphthalene-5,8-dione 14.2 grams of technical grade zinc dust purity) was added to a suspension of 38.3 grams of 2,3,4a,6,7,8a- 'hexachloro-ll,2,3,4,4a,8a-hexahydro-l,4-methanonaphthalene-5,8-dione in milliliters of acetic acid in 12 minutes at 50-93 C. with stirring and occasional cooling. The reaction mixture was stirred for an additional 15 minutes. A solution of 8 grams of chromium tr-ioxide (chromic acid) in 16 milliliters of water was then added to the stirred reaction mixture in 5 minutes at a temperature range of 5073 C. The reaction temperature was then held at 80-90 C. for an additional hour. The reaction mixturewas cooled, mixed with 280 milliliters of ice water, filtered and washed with 30 milliliters of methanol to give 27.1 grams of yellow product melting at 19 1200 C.

EXAMPLE XXIV In the foliage fungicide screen, three varieties of bean plants, which are hosts for four foliage fungus diseases, were employed. These hosts and pathogens are listed below. The chemicals were screened for general as well as specifice test control activity and, for phytotoxicity. Diseases and hosts are shown below:

Bean hosts: Pathogens Phaseolus vulgaris var. Uromyces phaseoli var. typ- Pinto ical (rust). Phaseolws vulgaris var. Erysiphe polygoni (pow- Black Valentine dery mildew). Phaseolus limensis val. Collectotrichum lindemu- Fordhook 242 thialzum (anthracnose).

Phytophrhora: phaseoli (downy mildew).

These four bean pathogens are of economic importance and represent each of four classes of fungi. Phytophthora phaseoli is closely allied with Phytophthora infestans, the important potato and tomato pathogen.

The test was carried out according to the following procedure. The test chemicals were prepared as 1% w./v. stock solutions in a solvent. The stock was diluted for spraying using a diluent consisting of distilled water plus solvent (1:1) or diluent consisting of distilled water plus two co-solvents (2:1:1). Triton X-155, at 0.0050.10% w., was used as a wetting agent for each concentration of toxicant. All chemicals were initially tested at a single concentration of 1000 p.p.m. Disease control being shown, the chemical were retested at 1000 p.p.m., and the next lowest dilution of 500 p.p.m. The chemicals were then retested in this fashion until the minimum effective concentration was determined. Phytotoxicity assessments are expressed as the maximum safe concentration.

Spray applications were made using a laboratory sprayer. The bean plants were selected for use at a stage when the two primary leaves were about three-quarters expanded. To facilitate deposit, theprimary leaves were oriented to a vertical position by pinning them to a small wire staff. Either the upper or lower epidermis of the leaf was exposed to the spray stream, depending on the surface to be inoculated.

With the mist-type spray and the diluent mixture which is applied, a drying interval of l-2 hours was sufiicient before inoculation with spore suspensions using a specially constructed atomizer. Inoculations with bean mildew were made by dusting conidia over treated plants in the greenhouse.

After 24 hours incubation at 19 C. and 100% humidity, the plants were removed to the controlled environment greenhouse for symptom development. Disease control and phytotoxicity assessments were made within seven 17 days. Of the greatest significance is the fact that compounds of the present invention are outstanding fungicides yet do not manifest significant phytotoxicity.

The following table summarizes the results of screening.

18 basis of the active ingredient. At all concentrations, 2,5,6 trichloro 1a,2,3,3a tetrahydro 3a-ethoxy-1,3- methano 1H cyclopropa(cd)naphthalene-4,7-dione was highly effective both as an apple scab protectant and as an TABLE I.-FOLIAGE FUNGIGIDE TESTS Disease Control Min. Efiective Concentration (p.p.rn.)

Phytotoxicity Max. Safe Concentration (p.p.m.)

U.p. O.l. B.V.

63 or less 63 or less 1, 000 1, 000 1, 000

125 63 or less 500 250 250 125 63 or less 1, 000 1,000 1, 000

1 P.p.= Phytophthom phaseoli (downy mildew of lime bean); E.p.=Erysiphe polygom (bean powdery mildew); U.p.= Uromyces phaseoli (bean rust);

O.l.= C'olletotrirhum lindemnthianum (bean anthracnose).

2 L=Lima bean; P=Pinto bean; BV =Black valentine bean.

EXAMILE XXV In advanced greenhouse tests 2,5,6-trichloro-1a,2,3,3atetrahydro 3a ethoxy-1,3-methano-lH-cyclopropa(ed) naphthalene-4,7-dione was tested for the control of row crop diseases of major economic importance. In this test, stock solutions of the test chemical were diluted with a mixture of 2, parts distilled water, 1 part acetone, 1 part isopropyl alcohol, and 0.01% Triton X-155 (alkyl aryl polyether alcohol). The following diseases and hosts were employed for foliage fungicide assessments; potato late blight (Phytophthora infestansP.i.), cucumber downy mildew (Pseudoperonospora cubensisP.c.), celery late blight (SeptOria apii gravelentis-S.a.), corn leaf blight (Helminthosporz'um turcicumH.t.), and cucumber anthracnose (Collectotrichum lagenarium-C. lag.). This test, the results of which are summarized in the following table, shows that 2,4,6-trichloro-1a,2,3,3atetrahydro 3a ethoxy-1,3-methano-1H-cyclopropa(cd) naphthalene-4,7-dione manifests outstanding activity as a foliage fungicide against row crop diseases. As amply shown by these tests, this test compound is particularly distinguished by its lack of phytotoxicity.

EXAMPLE XXVII 2,5,6 trichloro 1a,2,3,3a tetrahydro-3a-ethoxy-1,3- rnethano 1H cyclopropa(cd) naphthalene-4,7-dione was also evaluated in the field against apple scab. Six hundredths per cent by weight of the test chemical was mixed with 2 parts distilled water, 1 part acetone, 1 part isopropyl alcohol, and 0.01% Triton X-155. When this solution was sprayed on McIntosh and Red Delicious apple trees, no leaf scab was observed on the leaves. Moreover, only 2% of the McIntosh apples scabbed Whereas no scab was observed on the Red Delicious apples. When a stock solution containing 0.03% by weight of the test chemical was empl'oyed, only 2.5% leaf scab was observed on McIntosh apple leaves, and only 0.5% leaf scab was observed on Red Delicious leaves. Neither TABLE II Concentration of Phytotoxic Rating 1 Disease Control (percent) test Compound Based on Active' Ingredient (per- Celery Potato Cucumber Corn S.a. P.i. P.c. C.lag. Ht.

cent w./v.)

1 Rating scale of 0-4; 0=no injury; 4=plants killed. 2 Figures in parenthesis representnumber of tests.

EXAMPLE )QCVI the McIntosh nor the Red Delicious apples evidenced fruit scab at this concentration.

EXAMPLE XXVIII A. field test was also conducted employing 2,5,6-trichloro-1a,2,3,3a-tetrahydro 3 a ethoxy 1,3-methano- 1H-cyclopropa(-cd)naphthalene-4,7-dione to combat potato late blight (Phytophthora infestans). The test compound was employed at the rate of 0.5, 1.0 and 2.0

test chemical was varied from 0.2 to 0.01 on a percent 7 pounds of active ingredient per gallons of spray ap- EXAMPLE XXIX Not only are the compounds of the present invention effective fungicides when sprayed on plants but they may also be placed in the soil to combat soil-inhabiting phytopathogenic organisms. traordinary ellectiveness of compounds of the present invention in the soil, screening soil was sterilized by steam. Approximately 60 grams of the sterilized soil was then placed in 25 x 200 mm. test tubes and each tube sepa- In one test showing the exrately infested with Pythium ultimum or Fusarium oxysporum. After pea and sugar beet seeds were planted at approximately one-half inch ,below the soil surface, the soil'was drenched with a solution of the test chemical. 2,5,6 trichloro-la,2,3,3a-tetrahydro-3a-ethoxy-1,3-methano-IH-cyclopropa(cd)naphthalene-4,7-dione melting at 1723 C. was effective in combating both Pythium ultimum and F usarium oxysporum when employed at a concentration of only 60 ppm. 2,5,6-trichloro-la,2,3,3a-

tetrahydro-Ba-methoxy 1,3-methano-1H-cyclopropa(cd) naphthalene-4,7-dione was effective against these microorganisms at a concentration of ppm.

For horticultural purposes, the active compounds of the present invention may be used alone or in combination with other fungicidal, viricidal, insecticidal or acaricidal materials, the action on which may be either internal or external, with plant nutritives, plant hormones, and thelike. Wetting agents and, if necessary or desirable, stickers such as the heavy hydrocarbon oils with a minimum viscosity of 10 Engler at 50 C. can be present. The wetting agent must be non-reactive with the compounds of the present invention. Non-ionic surfactants seem preferable. If the toxic agents are employed in the form of emulsions or suspensions, for example, in water, solvents such as oils, emulsifiers, emulsion stabilizers, and the like may be added. Materials which suppress phytotoxic action may also be added if desired. For example, glucose is known to protect tomato plants against damage by certain substances having a phytotoxic elfect when employed in concentrated form.

For horticultural purposes, the compounds of the present invention may be applied by means of sprayin Spraying of the plants to be treated may be performed with aqueous emulsions, solutions, or suspensions of the active. agents. The spray liquid is generally applied at a rate of from about 75 to 150 gallons per acre. If spraying is effected with smaller quantities of liquid as in low volume spraying, high concentrations of the active agents should be employed. If desired, a minor amount of the order of about 0.01 to about 0.05% by weight'of name of Teepol and polyethylene glycol ethers of alkyl" phenols sold under the trade name of Triton X-lOO and Triton X-l SS. Preferable concentrate compositions comprising an active compound of the present invention and a suitable wetting agent are prepared, "and the con centrate is then dispersed in water prior to use.

A further form in which the fungicidal compounds of the present invention may be applied for horticultural purposes consists of solutions .ofthe active ingredient in suitable inert liquid or semi-solid diluents in which the.

active ingredient is present in molecularly dispersed form. The form in which the agents to be employed are applied naphtha, etc.

20' to the objects treated depends on the nature of the object and the purpose of the application.

Suitable inert solvents for the manufacture of liquid preparations should not be readily inflammable, as odorless as possible and without any toxic edect on humans and animals when properly used. Neither should they have a corrosive effect on the components of the prepares ti-ons or the material of the storage vessel. Examples of suitable solvents are high boiling oils, e.g., oils of vegeta ble origin such as cast-or oil, etc., and lower boiling solvents with a flash point of at least 30? C., suchuas carbon tetrachloride, ethylene dichloride, acetylene tetrachloride, hydrogenated naphthalene, alkylated naphthalene, sorbent Mixtures of solvents may also be used. Non-aromatic petroleum oils and xylene are commonly employed.

The active compounds of the present invention may also be applied for horticultural purposes in the form of dusts utilizing as the inert vehicle such materials as tr-icalcium phosphate, precipitated chalk, bentonite, kaolin, kieselguhr, etc. These compounds may also be employed in the form of aerosols. For this purpose the active ingredient is dissolved or dispersed in a solvent boiling below room temperature at atmospheric pressure.

The compounds of the invention have been found to have a surprisingly low mammalian toxicity. For example, the product illustrated by Example I has been fed to rats under standardized conditions for toxicity determination at rates up to 15 grams per kilogram without observing either chronic or acute toxicological reactions. Such products are thus useful where mammalian toxicity would be a drawback, e.g., for rotand mold-proofing materials to be brought into contact with humans, such as cloth, paper, wood, etc., and as anti-fungal agents in cosmetic preparations, lotions, and in soaps and other detergents. Indeed, their apparent low mammalian toxicity is one of their valuable attributes in all potential areas of use of the novel compounds of the invention.

The compounds of the present invention are active against a broad spectrum of microorganisms and bacteria in addition to the foliage and soil-inhabiting fungi already discussed. As a consequence of this unique activity, the compounds of the present invention may be employed in controlling microorganisms pathogenic to warm-blooded animals, such as man, livestock and domestic animals.

EXAMPLE In one series of tests showing this activity in vitro four species of bacteria were employed in a test tube dilution screen. In this test all organisms were incubated for 24 hours at 37 C. Emersons medium was employed for all types of bacteria. The results of these tests employing endiones of this invention are summarized in the followingtablfl,

End point in microorganism per ml. of medium (p.p.m.) Organism for complete inhibition A B G Gram-negative bacteria: Pseudomonas 1 ac! 50 Gram-positive bacteria:

Bacillus subiilts 2 50 2-5 Staphylococcus aureus 5 50 1. 5 Acid lastbacteria:

' Mycobacterium avium 10 50 10 Mycobacterium tuberculosis 10 Fungus: Fusarium orysporium 50 6-10 1 Test compound A2,5,6-tr1'chloro-1a,2,3,3a-tetrahydro-3areth0xy-1,3- methano-IH-cyclopropa(ed)naphthalene-4,7-dione. M.P. 172-3 C.

2 Test compound B2,5,6-trichloro-la 2,3,3a-tetrahydro-3a-isopropoxy- 1,3-n1ethano-1H-eyclopropa(ed) naphthalene-4,7-dione.

3 Test compound O-2,5 S-trichloro-la,2,3,3a-tetrahydre3ahexyloxy- 1,3-methano-llH-cyelopropafcd) naphtha1eue4,7dione.

21 EXAMPLE XXXi When ten mice -were treated with 2,5,6-trichloro- 1a,2,3,3a-tetrahydro-3a-hexyloxy-1,3-methano 1H cyclopropa(cd)naphthalene-4,7-dione at milligrams for kilogram body weight and l6 hours later challenged with a virulent strain of Listeria monocytogenes, 80% of the mice survived. Ten untreated mice similarly challenged gave complete mortality.

Three other groups of ten mice were treated with 2,5,6- trichloro 1a,2,3,3a-tetrahydro-3a-hexyloxy-1,3-methano- 1H-cyclopropa(ed)naphthalene-4,7-dione at 25 milligrams per kilogram body weight then inoculated with a highly infectious strain of Staphlococcus aureus 72, 96, and 120 hours, respectively, after treatment. The percentage of mice surviving the 72, 96 and 120 hour challenges were 40, 90 and 60, respectively. Three sets of untreated controls gave complete mortality when inoculated with the pathogen.

Ina further test, turkeys infected with pleuropneumonialike organism, Mycoplasma gallisepticum were. injected with 2,5,6-trichloro-1 a,2,3,3a-tetrahydro-3a-hexyloxy-1,3

methano-lH-cyclopropa(cd)naphthalener4,7-dione at 500 and 1500 milligrams per 'bird. The results. are summarized in the table below.

Dosage, milli- Percent with Percent with Compound grams/bird infected respiratory sinuses rales 2,5,6-trichloro-1a,2,3,- 3a-tetrahydro-3ahexyloxy-l,3-methano-lH-cyclopropa (cd)naphthalene- 4,7-dione 500 60 66 1, 500 28 22 Terramycin 500 35 50 Untreated contro1 65 80 EXAMPLE XXXII Compounds of the present invention have been shown to be active in controlling nematodes which infect mammals. Mice, heavily parasitized with the tapeworm, Hymenolepis nana and the pinworrn, Syphacia obvelara, were given the test compounds orally at 500 milligrams per kilogram. Three days after treatment the mice were sacrificed and the intestinal tract checked for the presence of parasites. All mice tolerated the test dosage of the compounds. The following table illustrates the activity of the compounds of this invention to control intestinal nematodes of mammals.

Thus, compounds of this invention are of value in the prophylaxis and treatment of certain diseases of warmblooded animals, such as man, livestock and domestic animals. According to the present invention compositions suitable for treatment of animals include in addition to the active compounds of the invention pharmaceutical or veterinary carriers which may either be solid or liquid materials. Preparations for oral injection can be liquids or solids or any combination of these forms, such as syrups, elixirs, emulsions, powders, capsules or tablets. Preparations for administration of the active agent in unit doses can take the form of compressed powders on tablets or of a powder enclosed in a suitable capsule of absorbable material such as .gelatin. The compressed powders, tablets, or capsules may also comprise suitable excipients and/ or diluents such as starch, lactose, stearic acid, magnesium stearate, dextrin, polyvinyl pyrrolidine or other diluents known to the pharmaceutical formulating art.

Preparations for parenteral administration may be in the form of sterile solutions or suspensions in such liquids as water, physiological saline, benzyl alcohol, ethyl oleate', corn oil, peanut oil, Carbowax 600 (water soluble polyethylene, approximate molecular weight 600), Carbow ax 400 (water soluble polyethylene, approximate molecular weight 400), glycerol monooleate, Methocil (water soluble methylcellsulose) and the like, dimethyl sulfoxide, and may contain soluble or insoluble diluents and/or solid' or liquid excipients.

Compositions according to this invention may be employed as feed supplements. Compounds of the present invention maybe mixed with an inert carrier or diluent. An inert carrier is one that is nonreactive with respect to the compounds of this invention and may be administered With safety to the animals to be treated. The carrier may be one of the ingredients of the animal feed or may be attapulgus clay, pyrophylite, bentonite and the like or may be of vegetable origin; corn cob meal, walnut shell flour, citrus meal, grain meal, grain hull meal or the like or may be of animal origin; bone meal, oyster shell meal, blood meal, fish meal and the like.

Compounds of this invention may be employed neat, with suitable carriers, or in combination with other medicants, vitamins, hormones, or growth stimulants.

The compounds of this invention may be mixed into the feed of animals, given in their drinking water, administered parenterally or intubated orally. As little as 0.1 milligram per kilogram of body weight may be sufiicient to protect the animal or to control certain pat-hogenic organisms or as much as milligrams per kilogram of body weight may be employed. As feed or water additives a dosage of as low as 0.5 part per million or as high as 500 parts per million of the compound may be required.

Compositions of compounds of this invention and suitable .inert carriers, vehicles, or diluents may contain as little as 0.0001% of the active ingredient or as much as 100% of the active compound.

I claim as my invention:

1. 3a substituted 1a,2,3,3a tetrahydro-1,3-methano- 1H-cyclopropa(cd)naphthalene 4,7 diones of the formula:

wherein each R, independently, is a member of the group consisting of hydrogen, middle halogen, unsubstituted a'lkyl of from one to ten carbon atoms, alkoxy of from one to ten carbon atoms, the alkyl moiety thereof being unsubstituted; R is a member of the group consisting 0L unsubstituted, mono-, and poly-(middle halogen)- substituted alkyl of from one to ten carbon atoms, allyl, benzyl, methoxyethyl, hydroxyethyl, dihydroxypropyl, tetrahydrofurfuryl, tetrahydropyranyl and 2,2-dimethyl- 1,3-dioxolan-4-ylmethyl.

2. Polyh'alo 1a,2,3,3a tetrahydro 3a alkoxy 1,3-

methane 1H cyc1opropa(cd)naphthalene-4,7-diones of the formula:

I 0 FY R\/,i I RI wherein R is middle halogen and R is a lky l of 1 to 10 carbpn :atoms.

3. Diones defined in claim 2 wherein R represents chlorine.

4. 2,5,6-ti'ich1o'ro-1a,2,3,3a-tetrahydre-3a ethoxy-1,3-

methano-1H-cyclopropa(cd naphthalene -4,7-di0ne.

5. 2,5;6-trichloro-1a,2,3,3'a-tetrahydfO-3a-methoxy- 1,3-methano-lH-CyclopropMcd) naphthalene-4,7-dione.

6. 2,5,6-trich1oro-1a,2,3,3a-tetrahydro-3a-propoxy- 1,3-methan0-1H-c:yclopr0pa(cd)naphthalene-4,7-dione.

7. 2,5,6-trichloro-121,2,3,3a-teirahydro3a-hexyloXy- 1, 3 -methano-1H-cyc1opropa(cd naphthalene-4,7-dione.

8. 2,5,6-trichl-oro-la,2,3,3a-tetrahydro-3a-chloroeth0xy-1,3-methano-1H-cyclopropa(cd) naphthalene- 4,7-dione. e

24 9. A dione defined by the formula:

5 II I Icl l $1 10 wherein R and R are alkyl of 1 to 10 car-hon atoms.

Referenees Cited by the Examiner i 1 UNITED STATES PATENTS I 2,475,288Tf7/19 49 Ladd '167 32 

1. 3A-SUBSTITUTED-1A,2,3,3A-TETRAHYDRO-1,3-METHANO1H-CYCLOPROPA(CD)NAPHTHALENE -4,7-DIONES OF THE FORMULA: 